Cellular and tissue changes that accompany tooth morphogenesis have been described in detail, but there is little information about the chemical influences which regulate this process. Epidermal growth factor (EGF) is a protein that is mitogenic for odontogenic cells in culture and that induces precocious eruption of incisors when injected into newborn rodents. These results suggest that EGF may play a role in regulating tooth development. In this study, we propose to examine in detail the effects of EGF on the odontogenic cells of incisors and molars. Newborn mice will be treated daily for one week with purified mouse EGF, the teeth will be decalcified, embedded in epon, and sectioned for analysis. Morphometric studies will be done to characterize the structural changes which occur in tooth morphology; the size of cellular and non-cellular compartments will be compared in teeth from control and EGF-treated animals and the number and size of cells in the proliferative and non-proliferative compartments will be analyzed. The effects of EGF on cell cycle kinetics will also be measured. Labelling index, mitotic index, frequency of labelled mitoses, and cell production rate, will be determined by autoradiography following injection of 3H-thymidine. Autoradiography will also be used to measure EGF-induced changes in the rate of dentin secretion as indicated by the incorporation of 3H-proline into collagen. The results of these experiments will explain the cellular changes which occur during EGF-induced precocious tooth eruption. The data should also provide new insight into the role that growth promoting molecules may pay in regulating tooth development.